Diffusion tensor imaging along the perivascular space: the bias from crossing fibres.

Non-invasive evaluation of glymphatic function has emerged as a crucial goal in neuroimaging, and diffusion tensor imaging along the perivascular space (DTI-ALPS) has emerged as a candidate method for this purpose. Reduced ALPS index has been suggested to indicate impaired glymphatic function. However, the potential impact of crossing fibres on the ALPS index has not been assessed, which was the aim of this cross-sectional study.

Alpha-synuclein seed amplification assay longitudinal outcomes in Lewy body disease spectrum.

Evidence from neuropathological cohorts indicates that a CSF α-synuclein (α-syn) seed amplification assay (SAA) may provide quantitative kinetic parameters correlating with α-syn pathology burden in patients with Lewy body disease (LBD). Studies are needed to assess their longitudinal trend during the pre-symptomatic and clinical disease phases and their correlation with measures of disease progression. We aimed to assess the baseline α-syn CSF SAA kinetic parameters, their longitudinal variations and associations with clinical outcomes in a cohort of longitudinally repeatedly sampled Lewy Body disease patients, including clinically unimpaired (asymptomatic LBD) and neurologically impaired individuals.

The combined pioglitazone and topiramate therapy for management of pediatric patients with severe MASLD.

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults.

Implementation of a Clinic-Based Yoga Program for Chronic Pain.

Purpose: Although many integrative therapies exist, studies increasingly demonstrate yoga can help change the negative neuroplastic effects experienced by people living with chronic pain. Despite encouraging findings, a gap exists in accessible yoga programs designed to meet the individual needs of those experiencing limitations from chronic pain. This study evaluated a yoga program designed for people living with chronic pain delivered in a health care setting.

Putaminal T1/T2-weighted ratio is increased in PSP compared to PD and healthy controls, a multi-cohort study.

Introduction: Differentiating Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is a common clinical problem. We aimed to apply the T-/T-weighted ratio imaging technique, based on standard clinical MRI, to reveal differences in neurodegeneration in three large cohorts.

Methods: Three cohorts, with a total of 405 participants (269 PD, 44 PSP, 38 MSA, 54 controls), were combined and T/T-weighted ratio image analyses were carried out.

The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases.

A positron emission tomography (PET) tracer detecting α-synuclein pathology will improve the diagnosis, and ultimately the treatment of α-synuclein-related diseases. Here we show that the PET ligand, [F]ACI-12589, displays good in vitro affinity and specificity for pathological α-synuclein in tissues from patients with different α-synuclein-related disorders including Parkinson's disease (PD) and Multiple-System Atrophy (MSA) using autoradiography and radiobinding techniques. In the initial clinical evaluation we include 23 participants with α-synuclein related disorders, 11 with other neurodegenerative disorders and eight controls.

DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease.

The diagnosis of Parkinsonian disorders is currently based on clinical criteria, which have limited sensitivity until most dopaminergic neurons are lost. Here we show that cerebrospinal fluid levels of DOPA decarboxylase (DDC) (also known as aromatic L-amino acid decarboxylase) can accurately identify patients with Lewy body disease (LBD) (area under the curve (AUC) = 0.89; P = 2.

Clinical effects of Lewy body pathology in cognitively impaired individuals.

There is poor knowledge about the clinical effects of Lewy body (LB) pathology in patients with cognitive impairment, especially when coexisting with Alzheimer's disease (AD) pathology (amyloid-β and tau). Using a seed amplification assay, we analyzed cerebrospinal fluid for misfolded LB-associated α-synuclein in 883 memory clinic patients with mild cognitive impairment or dementia from the BioFINDER study. Twenty-three percent had LB pathology, of which only 21% fulfilled clinical criteria of Parkinson's disease or dementia with Lewy bodies at baseline.

Multiple Mutations Associated with Emergent Variants Can Be Detected as Low-Frequency Mutations in Early SARS-CoV-2 Pandemic Clinical Samples.

Genetic analysis of intra-host viral populations provides unique insight into pre-emergent mutations that may contribute to the genotype of future variants. Clinical samples positive for SARS-CoV-2 collected in California during the first months of the pandemic were sequenced to define the dynamics of mutation emergence as the virus became established in the state. Deep sequencing of 90 nasopharyngeal samples showed that many mutations associated with the establishment of SARS-CoV-2 globally were present at varying frequencies in a majority of the samples, even those collected as the virus was first detected in the US.

Performance of [F]RO948 PET, MRI and CSF neurofilament light in the differential diagnosis of progressive supranuclear palsy.

Introduction: The diagnosis of progressive supranuclear palsy (PSP) is often challenging since PSP may clinically resemble other neurodegenerative disorders. Recently, the tau PET tracer [F]RO948, a potential new biomarker for PSP, was developed. The aim of this study was to determine the ability of three different biomarkers, including [F]RO948 PET, to distinguish PSP patients from healthy controls and from patients with α-synucleinopathies.

Performance of αSynuclein RT-QuIC in relation to neuropathological staging of Lewy body disease.

Currently, there is a need for diagnostic markers in Lewy body disorders (LBD). α-synuclein (αSyn) RT-QuIC has emerged as a promising assay to detect misfolded αSyn in clinically or neuropathologically established patients with various synucleinopathies. In this study, αSyn RT-QuIC was used to analyze lumbar CSF in a clinical cohort from the Swedish BioFINDER study and postmortem ventricular CSF in a neuropathological cohort from the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program (AZSAND/BBDP).

Midsagittal corpus callosal thickness and cognitive impairment in Parkinson's disease.

People diagnosed with Parkinson's disease (PD) can experience significant neuropsychiatric symptoms, including cognitive impairment and dementia, the neuroanatomical substrates of which are not fully characterised. Symptoms associated with cognitive impairment and dementia in PD may relate to direct structural changes to the corpus callosum via primary white matter pathology or as a secondary outcome due to the degeneration of cortical regions. Using magnetic resonance imaging, the corpus callosum can be investigated at the midsagittal plane, where it converges to a contiguous mass and is not intertwined with other tracts.

The Neuroinflammatory Acute Phase Response in Parkinsonian-Related Disorders.

Background: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings.

Objectives: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders.

Methods: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson's disease with dementia (PDD) (29).

Central nervous system monoaminergic activity in hip osteoarthritis patients with disabling pain: associations with pain severity and central sensitization.

Introduction: Monoaminergic activity modulates nociceptive transmission in the central nervous system (CNS). Although pain is the most disabling symptom of osteoarthritis (OA), limited knowledge exists regarding the CNS mechanisms that amplify pain and drive sensitization processes in humans.

Objectives: The main objective of this study was to evaluate associations between cerebrospinal fluid (CSF) monoamine metabolites, pain severity, and central sensitization in patients with OA undergoing total hip arthroplasty (THA).

Inflammation in Viral Vector-Mediated Ocular Gene Therapy: A Review and Report From a Workshop Hosted by the Foundation Fighting Blindness, 9/2020.

Subclinical or clinical inflammation often arises during ocular gene therapy with viral vectors. Understanding the biological bases and impacts on efficacy are important for clinical management and the improvement of future therapies.

Features That Aid Identification of Autoimmune Gastritis in a Background of Active Helicobacter pylori Infection.

Context.—: Helicobacter pylori-associated and autoimmune gastritis may coexist in a subset of patients who require treatment for both disorders.

Objective.

Plasma Phospho-Tau Identifies Alzheimer's Co-Pathology in Patients with Lewy Body Disease.

Background: Alzheimer's disease co-pathology is common in dementia with Lewy bodies and Parkinson's disease with dementia (Lewy body disease) and can reliably be detected with positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers. Recently developed blood biomarkers are more accessible and less expensive alternatives.

Objective: To investigate if plasma phospho-tau217 and phospho-tau181 can detect Alzheimer's pathology in Lewy body disease with dementia.

Differential expression of cerebrospinal fluid neuroinflammatory mediators depending on osteoarthritis pain phenotype.

Neuroinflammation is implicated in the development and maintenance of persistent pain states, but there are limited data linking cerebrospinal fluid (CSF) inflammatory mediators with neurophysiological pain processes in humans. In a prospective observational study, CSF inflammatory mediators were compared between patients with osteoarthritis (OA) who were undergoing total hip arthroplasty due to disabling pain symptoms (n = 52) and pain-free comparison controls (n = 30). In OA patients only, detailed clinical examination and quantitative sensory testing were completed.

Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson's disease.

Objectives: Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD.

Methods: We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing.

Cerebrospinal fluid levels of neurogranin in Parkinsonian disorders.

Background: CSF concentration of neurogranin has been suggested as a biomarker for synapse dysfunction.

Objectives: To investigate CSF neurogranin in parkinsonian disorders compared to controls and Alzheimer's disease and the possible correlations between neurogranin and cognitive and motor impairment.

Methods: We included 157 patients with PD, 29 with PD with dementia, 11 with dementia with Lewy bodies, 26 with MSA, 21 with PSP, 6 with corticobasal syndrome, 47 controls, and 124 with Alzheimer's disease.